Abstract Background Disruption to the intestinal barrier is central to inflammatory bowel disease (IBD). Reliable circulating biomarkers of barrier dysfunction remain lacking. Ceramides and related sphingolipids are key signaling molecules involved in barrier integrity and have been shown to be dysregulated in IBD. We aimed to compare plasma sphingolipid profiles among patients with ulcerative colitis (UC), Crohn’s disease (CD) psoriatic arthritis (PsA) and healthy volunteers to assess whether specific sphingolipid alterations may reflect intestinal barrier dysfunction in IBD. Methods We collected plasma samples from 50 healthy volunteers, 71 UC patients, 68 CD patients and 110 PsA patients, resulting in a total of 630 samples including longitudinal visits (approx. every 3 months when feasible). Routine venous blood (approx. 9 ml) was centrifugated (10 min, 4 °C, 2000g), plasma aliquots (1mL) were stored at -80 °C. Sphingolipid quantification (spingoid bases and ceramides including lactosylceramides) was performed using liquid-liquid extraction followed by two separate LC-MS/MS methods. Statistical comparisons were made between IBD vs healthy vs PsA cohorts; subgroup analysis included UC vs CD. Results IBD patients were significantly younger and had lower BMI compared to PsA patients; sex distribution was comparable between groups. The lactosylceramide species LacCer d18:1/16:0 was significantly elevated in IBD patients compared to healthy volunteers and PsA patients. This difference was most pronounced in the UC cohort (Figure 1). When analysing all available time-points per patient, LacCer d18:1/16:0 remained significantly higher in UC patients than in the other groups. These findings suggest a specific elevation of this sphingolipid in IBD, particularly in UC. Conclusion Our interims analysis indicates that plasma LacCer18:1/16:0 may serve as a promising biomarker to distinguish IBD (especially UC) from other immune-mediated diseases and healthy individuals, potentially reflecting ongoing intestinal barrier dysfunction. Further validation including correlation with established barrier markers, disease activity indices and endoscopic/mucosal outcomes is warranted. Conflict of interest: Dr. Kubesch, Alica: No conflict of interest Gurke, Robert: No conflict of interest Teske, Michael: No conflict of interest Thomas, Dominique: No conflict of interest Mohs, Kathleen: No conflict of interest Lande, Raul: No conflict of interest Figat, Magdalena: No conflict of interest Köhm, Michaela: No conflict of interest Behrens, Frank: No conflict of interest Zeuzem, Stefan: No conflict of interest Blumenstein, Irina: Consulting and/or speker fees: AbbVie, Alfasigma, Amgen, Biogen, CED Service GmbH, Falk, Ferring, Fraunhofer, Johnson & Johnson, Pharmacosmos, Pfizer, Sanofi, Takeda, Tillotts Research grants: Fraunhofer ITMP, Sanofi
Kubesch et al. (Thu,) studied this question.